Optimal elimination of leukemic T cells from human bone marrow with T101-ricin A-chain immunotoxin

作者：P Casellas, Xavier Canat, AA Fauser, Olivier Gros, G Laurent, P Poncelet, FK Jansen · 发表于：Blood · 年份：1985 · DOI：10.1182/blood.v65.2.289.289 · 被引用次数：66 · 研究领域：Toxin Mechanisms and Immunotoxins、Transgenic Plants and Applications、CAR-T cell therapy research

In view of bone marrow purging before autologous transplantation in T cell malignancies, an anti-human T cell immunotoxin (IT) has been prepared by coupling ricin A-chain to the monoclonal antibody T101 that binds the T1 differentiation antigen expressed by T lymphocytes as well as by T cell-derived hematologic malignancies. Using a sensitive and reliable clonogenic assay, optimal conditions were defined for the elimination of clonogenic human T leukemic cells among bone marrow cells. Maximal cytoreduction was obtained with IT at a dose of 2 micrograms/mL in the presence of 10 mmol/L NH4Cl. This treatment led to the reduction of more than six orders of magnitude of T101-positive clonogenic leukemic cells, with no harm to T101-negative cells. Moreover, we observed no toxicity of IT to human hematopoietic stem cells (CFU-GEMMT) derived from bone marrow of healthy volunteers. Thus, pretreatment of bone marrow samples with IT plus NH4Cl offers a safe, simple, reliable, and highly efficient means to eliminate undesirable leukemic T cells from the graft.